Insulin gene transcription is mediated by interactions between the p300 coactivator and PDX-1, BETA2, and E47

Y. Qiu, M. Guo, S. Huang, R. Stein

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Pancreatic β-cell-type-specific expression of the insulin gene requires both ubiquitous and cell-enriched activators, which are organized within the enhancer region into a network of protein-protein and protein-DNA interactions to promote transcriptional synergy. Protein-protein-mediated communication between DNA-bound activators and the RNA polymerase II transcriptional machinery is inhibited by the adenovirus E1A protein as a result of E1A's binding to the p300 coactivator. E1A disrupts signaling between the non-DNA-binding p300 protein and the basic helix-loop-helix DNA-binding factors of insulin's E-element activator (i.e., the islet-enriched BETA2 and generally distributed E47 proteins), as well as a distinct but unidentified enhancer factor. In the present report, we show that E1A binding to p300 prevents activation by insulin's β-cell-enriched PDX-1 activator. p300 interacts directly with the N-terminal region of the PDX-1 homeodomain protein, which contains conserved amino acid sequences essential for activation. The unique combination of PDX-1, BETA2, E47, and p300 was shown to promote synergistic activation from a transfected insulin enhancer-driven reporter construct in non-β cells, a process inhibited by E1A. In addition, E1A inhibited the level of PDX-1 and BETA2 complex formation in β cells. These results indicate that E1A inhibits insulin gene transcription by preventing communication between the p300 coactivator and key DNA-bound activators, like PDX-1 and BETA2:E47.

Original languageEnglish (US)
Pages (from-to)412-420
Number of pages9
JournalMolecular and cellular biology
Volume22
Issue number2
DOIs
StatePublished - Jan 12 2002

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Insulin
Genes
Proteins
DNA
Adenovirus E1A Proteins
Homeodomain Proteins
RNA Polymerase II
Amino Acid Sequence
Carrier Proteins
Gene Expression

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

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title = "Insulin gene transcription is mediated by interactions between the p300 coactivator and PDX-1, BETA2, and E47",
abstract = "Pancreatic β-cell-type-specific expression of the insulin gene requires both ubiquitous and cell-enriched activators, which are organized within the enhancer region into a network of protein-protein and protein-DNA interactions to promote transcriptional synergy. Protein-protein-mediated communication between DNA-bound activators and the RNA polymerase II transcriptional machinery is inhibited by the adenovirus E1A protein as a result of E1A's binding to the p300 coactivator. E1A disrupts signaling between the non-DNA-binding p300 protein and the basic helix-loop-helix DNA-binding factors of insulin's E-element activator (i.e., the islet-enriched BETA2 and generally distributed E47 proteins), as well as a distinct but unidentified enhancer factor. In the present report, we show that E1A binding to p300 prevents activation by insulin's β-cell-enriched PDX-1 activator. p300 interacts directly with the N-terminal region of the PDX-1 homeodomain protein, which contains conserved amino acid sequences essential for activation. The unique combination of PDX-1, BETA2, E47, and p300 was shown to promote synergistic activation from a transfected insulin enhancer-driven reporter construct in non-β cells, a process inhibited by E1A. In addition, E1A inhibited the level of PDX-1 and BETA2 complex formation in β cells. These results indicate that E1A inhibits insulin gene transcription by preventing communication between the p300 coactivator and key DNA-bound activators, like PDX-1 and BETA2:E47.",
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Insulin gene transcription is mediated by interactions between the p300 coactivator and PDX-1, BETA2, and E47. / Qiu, Y.; Guo, M.; Huang, S.; Stein, R.

In: Molecular and cellular biology, Vol. 22, No. 2, 12.01.2002, p. 412-420.

Research output: Contribution to journalArticle

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T1 - Insulin gene transcription is mediated by interactions between the p300 coactivator and PDX-1, BETA2, and E47

AU - Qiu, Y.

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AU - Stein, R.

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